New research shows MDMA and psilocybin may restore neural flexibility in people with PTSD, thereby helping the brain unlearn fear and relearn safety.
For researcher Lynnette Averill, the quest to find a treatment for post-traumatic stress disorder (PTSD) is deeply personal. Averill's father served as an enlisted infantryman with the U.S. Marine Corps in Vietnam and struggled to cope with his war experiences when he returned home. After years of ineffective treatments, he died by suicide when Averill was three.
Driven by a mission to support veterans' mental health, Averill trained as a psychologist and began working with people with PTSD — a condition that affects more than 12 million Americans in any given year. Victims of violence, abuse and accidents can experience post-traumatic symptoms such as persistent flashbacks, hypervigilance, and entrenched negative beliefs about themselves and their environment.
"People can be very stuck in black-and-white thinking, such as, 'I'm a bad person,' 'I deserve this,' 'the world is dangerous," Averill, a clinical research psychologist at the Baylor College of Medicine in Texas, said during a panel discussion at the Psychedelic Science conference in Denver in June 2025.
The root of these symptoms lie in how trauma shapes changes in the brain in the weeks and months after a frightening event. The brain's fear center — the amygdala — becomes hyperactive, constantly signaling danger, while the brain regions responsible for contextualizing memories and managing emotional responses become less active and less able to counterbalance those fear signals. Traditional therapies, such as antidepressant medications and trauma-focused psychotherapies, help only a fraction of patients and can take months to be effective.
"For many people with PTSD, they simply aren't enough, " Averill told Live Science.
Consequently, Averill is one of a group of researchers who are exploring a new potential avenue for treating PTSD: psychedelics. Psychedelic-assisted psychotherapy, using MDMA or psilocybin, may act on the brain systems disrupted in PTSD, rather than simply treating the symptoms.
The early findings have been positive: A recent clinical trial showed that 67% of patients who received MDMA-assisted therapy no longer met PTSD criteria after treatment, compared with 32% in the placebo group, and clinical trials investigating psilocybin's potential to treat the condition are showing promise.
Averill is currently leading a pioneering Texas state-funded clinical trial investigating psilocybin for veterans with PTSD and has seen how quickly the drugs can act.
"There's potential for people to feel that the needle has moved in hours," Averill said. "And that is just quite literally lifesaving."
How trauma changes the brain
PTSD shares symptoms with depression and anxiety. Yet it is characterized by a response to a single trauma or set of traumatic events. Such experiences spark fear and often challenge an individual's core beliefs that the world is a just, safe and predictable place. People with PTSD can feel helpless and without agency.
It's normal for people who have endured traumatic events to experience these symptoms for a short time, and for most people, they resolve within a week or two, clinical psychologist Gregory Fonzo, a co-director of the Charmaine and Gordon McGill Center for Psychedelic Research and Therapy at the University of Texas at Austin's Dell Medical School, told Live Science. But a subset of people get stuck.
What Happens in the Brain During a PTSD Episode?
In PTSD, the amygdala remains stuck in an overactive state, causing symptoms like hyperarousal, irritability and being easily startled. At the same time, the prefrontal cortex, which normally calms those alarms, becomes underactive, leaving the amygdala's overreactive fear response unchecked.Neuroimaging has shown that PTSD is associated with a reduced volume of the hippocampus, which is the brain region that processes the context — the where, when and circumstances — of an event.
In normal circumstances the hippocampus can discriminate between real and perceived danger. For example, it will categorize the sound of a car backfiring in an everyday environment differently than the blast of gunshot, which occurred specifically in a war zone. But a diminished hippocampus could make it harder for patients to distinguish between the two.
Clinical Trials
Clinical trials have found psilocybin, the main psychoactive ingredient in magic mushrooms, to be a promising therapy for treatment-resistant anxiety and depression, and studies conducted on animals have pointed to its potential for treating PTSD.
A study on mature adult mice demonstrated that MDMA temporarily reopens a critical period for where the brain is sensitive to learning that social behaviors are beneficial by inducing structural and functional changes in the brain’s reward circuits. This enhanced sensitivity allows the adult brain to re-encode social cues as intrinsically rewarding and safe, facilitating the re-learning of trust and attachment for up to two weeks after a single dose, the researcher theorize.
What the Trials Have Shown
Several trials are underway to investigate psilocybin as a treatment option for PTSD. In August 2025, biotechnology company Compass Pathways published its findings on a trial designed to test the safety of psilocybin for PTSD. The small safety study wasn't designed to measure effectiveness. Nevertheless, participants seemed to show an immediate reduction in PTSD symptoms after a single 25-milligram dose of the company's synthetic psilocybin. Clinicians reported the improvements had endured when tested 12 weeks later.
Challenges
Clinical psychologist Gregory Fonzo, a co-director of the Charmaine and Gordon McGill Center for Psychedelic Research and Therapy at the University of Texas at Austin's Dell Medical School, believes the answer lies in the expansion of funding for clinical trials, but research in psychedelics still faces steep hurdles. Both MDMA and psilocybin are listed as Schedule I substances in the U.S. — a federal classification reserved for drugs considered to have a high potential for abuse and no accepted medical use. That label makes studying them a bureaucratic nightmare, as researchers must navigate complex regulatory approvals and secure special licenses just to handle the compounds.
FDA Not Moving Quickly Enough
For veterans who are experiencing suicidal thoughts as part of their PTSD, finding interventions that spur rapid change could be key, Weiss said. Despite the compelling findings, the regulatory approval of psychedelic treatments for PTSD is moving slowly. In August 2024, the U.S. Food and Drug Administration declined to approve MDMA-assisted therapy for PTSD, citing concerns over the study design and blinding procedures. Many have been frustrated about the decision not to approve the treatment with guardrails, or for a subset of people who really need it.
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